A multi-million dollar effort to create a technology platform to map the human interactome is underway in Canada with an eye to making it international.
Last month the Canada Foundation for Innovation awarded C$9.16 million ($7.89 million) to a national initiative to create a technology platform, bringing the total funding for the project to C$22.9 million ($19.7 million).

A total of 12 universities throughout Canada will be working on the interactome project.

Once the national technology platform becomes operational, the plan is to bring in institutions and partners from around the globe in an international push to create a complete set of cellular interaction networks.

In an interview with ProteoMonitor this week, Benoit Coulombe, who is heading the Canadian work and is a professor and director of the Proteomics Discovery Platform at the Institut de Recherches Cliniques de Montreal, said that the national technology platform comprises the 12 universities along with their instruments, methods, workflows, and expertise in elucidating the human interactome.

Much of the funding will be directed at purchasing new equipment and renovating facilities. The C$9.16 funding from CFI, an independent corporation created by the Canadian government, is for infrastructure. The remaining C$13.74 million, which comes from other partners such as the province of Quebec and companies such as Thermo Fisher Scientific, also will be used for infrastructure costs, not operational expenses, Coulombe said.

While the 12 universities are already mapping the human interactome, the national initiative brings them together in a collaborative mode that can lead to greater efficiency, more reliable results, and generally better science, Coulombe said.

“The idea of this technology platform is that we put together 12 universities across Canada … that already have activities in protein-protein interaction or interactome studies,” he said. In a virtual manner, “these 12 institutions [will now] sit around the same table and plan their activities relating to protein-protein, protein-RNA interaction studies, et cetera. … Now we have a coordinated platform and now we can plan the equipment [and] the technology pipeline that we want to run.”

New methods development, especially in computational approaches, will also be part of the initiative.

The schools involved in the effort are IRCM, which is affiliated with the University of Montreal; Centre for Cellular and Biomolecular Research at the University of Toronto; Samuel Lunenfeld Research Institute at the Mt. Sinai Hospital; the Ottawa Institute of Systems Biology at the University of Ottawa; the Université de Sherbrooke; Dalhousie University; the University of Victoria; the University of British Columbia; the University of Manitoba; the Institut de Recherché en Immunologie et en Cancérologie at the University of Montreal; McGill University; and the Université Laval.

Because each participating institution has its own area of expertise, the initiative will allow researchers to tap into information that they otherwise might not have access to, Coulombe said. In addition, the organizational structure will facilitate interlaboratory work among the participants, which could improve reproducibility, he added.

When different schools perform a similar experiment, it will be important that common standard operational procedures are in place and followed “so that the data that comes out of the many sites…are comparable,” Coulombe said.

“The only way to achieve this is through communication between the sites. So if some of the sites combine their efforts in [a] project, we have to be able to tell the funders that when we do the same type of experiments in different locations, we’re doing it in a way that the data can be compared, is reproducible, [and] is complementary but can be put together,” he said. “So this is one of the important virtues of this type of platform.”

The initiative is currently performing a multi-site pilot project comparing affinity purification techniques. Each site, using similar equipment and analytical methods for the same proteins, is generating data, which will then be analyzed to determine what steps need to be taken to resolve differences between different labs.

In addition, they are investigating methods aside from mass-spec based technologies to monitor protein-protein interactions such as yeast 2-hybrids and luminescence-based mammalian interactome technology, or LUMIER, Coulombe said.

Within six months, most of the new equipment should be installed and the national platform should be “90 percent operational.” In a year, “we plan to have operational funding for at least one big interactome project,” he said.

If that happens, it would be one of the few examples of such a project. While there have been calls in the past for a large-scale human interactome mapping effort, such proposals have failed to take flight and most of the current work has been confined to individual labs. According to Tony Pawson of the Samuel Lunenfeld Research Institute and a participant in the Canadian effort, only about 5 percent of the human interactome has been mapped to date.

The most prominent proponent of a coordinated interlaboratory approach to describing the human interactome has been Marc Vidal, an associate professor of genetics at the Harvard Medical School, who in 2006 published an article in The Scientist advocating for a $100 million investment into a large-scale human interactome mapping effort. While the funding agencies never took him up on his advice, a number of smaller individual efforts have been started since then, he told ProteoMonitor.

The Center for Cancer Systems Biology at the Dana Farber Cancer Institute, of which Vidal is director, has also adopted the Human Interactome Mapping Project as its flagship project.

“We’re not quite there yet … if you were to compare us to the genome sequencing project at its peak, but it’s definitely starting to crystalize a bit,” he said. “People are getting together, people are publishing four, five, six groups together. … I also think that the field as a whole is already past the single lab, single R01 [stage].”

In January, he and a cadre of other collaborators published a series of articles in Nature Methods describing research into the interactomes of various organisms.

The Systems Biology Center New York has also been exploring the idea of a Quantitative Human Interactome Project to “experimentally obtain kinetic constants for cellular interactions between all of the proteins encoded by the human genome and construct a database of these parameters,” according to a report it released in March 2008.

Coulombe said that the Canadian initiative is the only one he knows of that pulls together the resources of so many institutions and directs it at the human interactome.

But at a time when other similar projects, such as mapping the human proteome, have failed to gain any traction, and protein-protein interactions within the human model are still poorly understood, are Coulombe and his peers jumping ahead of themselves with their ambitions to map the human interactome, which looks not only at protein-protein interactions but also at protein-DNA and protein-RNA interactions?

They don’t see it that way. Pawson said that the technology has reached the stage where “it’s really feasible to think about doing these things on a large scale, and also very importantly, people who use different approaches … are starting to talk to each other much more extensively.”

Indeed, while the funding announced last week focuses on building the national technology platform, Coulombe and others in the initiative are already looking ahead to a large-scale effort that would involve researchers from across the globe to map the human interactome. That effort is called the International Interactome Initiative, or I3.

“This is one of the projects that we hope will be supported by the platform,” Coulombe said. “The national platform is the technology platform in Canada that will serve in the international interactome initiative.”

The Canadian initiative and the proposed I3 plan comes out of a project called the Human Proteotheque Initiative that Coulombe has been working on for several years to chart protein interactions that regulate cell growth, differentiation, and disease progression [see PM 08/02/07].

“What you see now [with I3] is the evolution of this initiative,” Coulombe said. “We’re building our way to the interactome.”

He and others involved in trying to get I3 off the ground have created a steering committee “that includes key players in the interactome field from the US, from Europe and from Canada,” that is exploring funding opportunities for the project and setting scientific objectives, Coulombe said, adding that he hopes to have funding for I3 secured next year so that research can begin in early 2011.

“With this international consortium, we feel that if we have appropriate funding, by joining efforts and technologies such as affinity purifications, mass spectrometry, yeast 2-hybrids, protein complementation assays, LUMIER … in five years we [could] have a draft map of the interactome with pretty much full coverage,” Coulombe said.